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Biomedical subjects

P Edwards

Publications and source records attributed to P Edwards.

At least 19 recordsLinked to original sources

Postoperative radial nerve paralysis caused by fracture callus.

This is a case of late-onset (6 weeks) radial nerve paralysis following open reduction and internal fixation of a comminuted distal humerus fracture. A transected radial nerve within the callus was found at reoperation. The mechanism of transection was thought to be repetitive motion of the nerve across an edge of new bone. The nerve was repaired and tendon transfers done subsequently with less than full functional recovery at 16 months. No such case has been previously reported.

Adult

Synthesis of optically pure C alpha-methyl-arginine.

Optically pure L-(+)-C alpha-methyl-arginine and D-(-)-C alpha-methyl-arginine were synthesized. Experimental results indicated that DL-C alpha-methyl-arginine methyl ester could be resolved by trypsin, but workup posed a technical difficulty. Chemical resolution at the stage of DL-C alpha-methyl-ornithine, followed by selective guanidination using N,N'-di-Cbz-S-methylisothiourea and hydrogenolysis provided a effective and practical method for the synthesis of optically pure C alpha-methyl-arginine.

Arginine

In-vivo pharmacological studies of 2-N-carboxamidinonormianserin, a histamine and 5-hydroxytryptamine antagonist lacking central effects.

The in-vivo pharmacological properties have been examined of FCC5 (2-N-carboxamidino-1,2,-3, 4, 10, 14b-hexahydrodibenzo (c.f.) pyrazino (1, 2-alpha)azepine hydrochloride), a guanidino analogue of mianserin. FCC5 (30-100 micrograms kg-1, i.v.) caused long-lasting (> 1 h) attenuation of histamine- and 5-hydroxytryptamine (5-HT)-induced bronchoconstriction in the anaesthetized guinea-pig. FCC5 (< or = 1 mg kg-1, i.v.) had no effect on submaximal bronchoconstrictor responses caused by i.v. acetylcholine or the thromboxane A2-mimetic U46619 ((15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid). The pressor effects of 5-HT in anaesthetized and pithed rats were inhibited by FCC5 (0.3-1.0 mg kg-1, i.v.). Higher doses of FCC5 (3 mg kg-1, i.v.) reduced bradycardia and depressor responses to 5-HT in anaesthetized rats. In anaesthetized cats and rats and also pithed rats, FCC5 (0.1-1.0 mg kg-1, i.v.) caused sympathomimetic effects as demonstrated by pressor responses and tachycardia. FCC5 (0.1-0.3 mg kg-1, i.v.) inhibited pressor responses to tyramine whereas those to noradrenaline and sympathetic nerve stimulation were potentiated. Oedema in the rat paw caused by intraplantar 5-HT was inhibited by FCC5 (ID50 0.76 mg kg-1, i.p.; and 2.7 mg kg-1, p.o.). In decerebrate rats which had been spinalized at T6-8, fenfluramine-induced facilitation of the flexor reflex of the anterior tibialis muscle was inhibited by mianserin (ID50 0.36 mg kg-1, i.p.) but not by FCC5 (< or = 3 mg kg-1, i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Hyperglycemic athymic nude mice: factors affecting in vitro insulin secretion.

The strain of athymic nude male mice (ANM) developed at the University of Southern California (USC) exhibits spontaneous hyperglycemia and relative hypoinsulinemia in vivo. To investigate factors that influence insulin secretion in this animal model of non-insulin-dependent diabetes mellitus, we utilized the isolated perfused mouse pancreas of the ANM-USC and control BALB/c mice. We compared in vitro glucose-induced insulin secretion in ANM-USC and control mice, inhibition of secretion by somatostatin, and variability of insulin secretion over the two-year period it took to complete these experiments. Glucose-induced insulin secretion from the isolated pancreas was biphasic in both ANM-USC and controls. Insulin secretion was quantitatively equal to or greater than control mice, depending on the phase of secretion analyzed and the source of the control mice. In contrast to pancreases of control mice, insulin secretion from ANM-USC pancreases was relatively resistant to inhibition of insulin secretion by somatostatin. Variability in insulin secretion over the two years in which these experiments were performed was greater from pancreases of control than that observed from pancreases of the ANM-USC. The hyperglycemic ANM-USC mouse does not demonstrate diminished insulin secretion in vitro yet is relatively hypoinsulinemic in vivo. Thus circulating factors other than somatostatin might contribute to the insulinopenic stage in this animal model.

Animals

A quantitative analysis of matrix alignment in ligament scars: a comparison of movement versus immobilization in an immature rabbit model.

This investigation quantified the alignment of fibrillar matrix in normal rabbit medial collateral ligaments (MCLs) and in healing MCLs from animals treated with or without knee immobilization. Twenty-four immature female rabbits were given complete midsubstance injuries to their right MCLs. Fifteen of them had that knee pin immobilized in flexion, while the remaining nine were allowed unrestricted cage activity. Animals were sacrificed in groups of three at intervals of 3, 6, or 14 weeks after injury, and both healing MCLs and unoperated contralateral controls were fixed in situ for subsequent removal, freeze-fracture, and preparation for scanning electron microscopy (SEM). A random sampling of SEM photographs followed by automated, statistically validated image processing was used to quantify alignment of matrix in all samples. Results showed that nonimmobilized MCL scars in this model do remodel over 14 weeks of healing, returning to normal alignment values in that time. Surprisingly, MCL scars in immobilized knees were even better, with mean matrix alignments falling statistically within normal MCL limits at all healing intervals studied. If not due to an unknown sampling or fixation artifact, these results suggest that gross knee flexion and extension is not a prerequisite for scar matrix alignment in this immature model of ligament healing.

Animals

Outcome 1 to 3 years after severe traumatic brain injury in children and adolescents.

This study reports a consecutive series of 220 children and adolescents who sustained traumatic brain injury (BI) and were admitted to a comprehensive paediatric rehabilitation programme. Progress in areas of mobility, activities of daily living, education and cognitive function were documented for up to 3 years after the injury. Physical recovery was most rapid in the first years and cognitive and language gains generally occurred later, even up to 3 years after the injury. Cognitive assessment at the time of admission proved helpful in predicting outcome; of those patients admitted in a conscious state only one remained dependent for any aspect of self care. Even for those admitted unconscious at a median of 62 days after injury there was good potential for recovery with 27-43 per cent achieving independence in the activities of daily living. For those still unconscious at 6 months, 72 per cent remained vegetative and none achieved the highest cognitive level. Overall, 14 per cent returned to regular education while 25 per cent remained incapable of any educational programme. In a well planned and multidisciplinary rehabilitation programme, patients with severe BI have potential for continued recovery and measurable improvement for at least 3 years. The emphasis should be targeted on differing areas of the therapy programme at different phases of recovery. A realistic appraisal of the ultimate potential for recovery can usually be made by 6 months.

Accidents, Traffic

A transducing bacteriophage for Caulobacter crescentus uses the paracrystalline surface layer protein as a receptor.

The bacteriophage phi Cr30, a transducing phage for Caulobacter crescentus strains, required the paracrystalline surface (S) layer for infectivity. Wild-type strains were phage resistant when rsaA, the gene for the 130K S-layer protein, was interrupted with an antibiotic resistance cassette. Strains that had lost the S layer by mutation were phage resistant, as were mutants that produce an S layer but which do not attach the structure to the cell surface. Phage sensitivity was restored to 130K-protein-deficient strains by introducing rsaA on a plasmid. Spontaneous phage-resistant strains produced expected phenotypes as follows (in order of decreasing frequency): S-layer cell attachment defects, no S layer, or an S layer that was wild type in appearance.

Bacteria, Aerobic

Outbreak of human calicivirus gastroenteritis in a day-care center in Sydney, Australia.

Between January and March 1988, an outbreak of gastroenteritis occurred among children and staff at a day-care center in Sydney, New South Wales, Australia. Over an 11-week period, 53 persons had 101 episodes of gastroenteritis; some patients had 5 separate episodes. The principal etiologic agent in the outbreak, human calicivirus (HCV), was detected by electron microscopy in 32% of fecal specimens from children and staff members with symptoms but in only 8% of asymptomatic individuals (P less than 0.01). HCV was confirmed by both an enzyme immunoassay and solid-phase immune electron microscopy. HCV infection was a particular problem in infants, who had the highest age-specific attack rates, had the greatest symptomatic/asymptomatic infection ratio, and were most likely to have a second symptomatic episode. The mode of transmission of this virus was not identified, and extensive efforts to control the 11-week outbreak had little effect. Prolonged excretion of HCV by some symptomatic patients and high rates of asymptomatic infection may have contributed to the extended duration of the outbreak. HCV may be a common cause of gastroenteritis in children that is under-recognized because of insensitive methods of detection.

Australia

Metabolism of pyridoxine in mild metabolic hyperoxaluria and primary hyperoxaluria (type 1).

Plasma pyridoxine metabolites in plasma and 4-pyridoxic acid excretions in urine were measured in normal subjects, in 7 patients with type-1 hyperoxaluria and in 8 patients with mild metabolic hyperoxaluria, while receiving various doses of pyridoxine. Compliance with ingestion of pyridoxine was verified by measuring urinary 4-pyridoxic acid. In the normal subjects the maximum level of pyridoxal phosphate was obtained after only 10 mg/day of pyridoxine. The patients were divided into nonresponders, good responders and poor responders to pyridoxine according to the fall in urinary oxalate and glycollate excretions. In patients taking pyridoxine, the plasma pyridoxal phosphate levels were as for normal subjects in primary hyperoxaluria, lower than for normal subjects in mild metabolic hyperoxaluria (p less than 0.01), and in the latter group lower in partial responders than in good responders (p = 0.04). Hence in mild metabolic hyperoxaluria there may be difficulty in converting pyridoxine to pyridoxal phosphate.

Chromatography, High Pressure Liquid

An experimental model to assess the value of laser angioplasty in the management of atheromatous disease of the carotid bifurcation.

Laser angioplasty is used to vaporize atheroma in limb arteries. The present investigation was undertaken to determine the nature, size and quantity of particulate matter generated, and the appearance of the intima of a carotid artery model after laser treatment. Particulate matter was not significantly increased following treatment of 39 autopsy carotid bifurcations, but superficial plaques were vaporized and the surface of fibrous lesions glazed. It is anticipated that atheromatous carotid vessels would be rendered less thrombogenic and the risk of cerebral embolism reduced later angioplasty.

Aged

6-(substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase. III. Structure-activity relationships of the 5-membered heterocyclic derivatives.

Sodium (5RS)-Z-6-(heterocyclylmethylene)penem-3-carboxylates (2) are a series of extremely potent inhibitors of bacterial beta-lactamases. A variety of 5-membered heteroaromatic derivatives have been prepared and structure-activity studies reveal a preferred substituent orientation. One of these derivatives, the 1-methyl-1,2,3-triazolyl compound (5m) is a more potent synergist of amoxycillin than clavulanic acid, sulbactam or tazobactam.

Amoxicillin

Burnout among staff members at community residential facilities for persons with mental retardation.

The Maslach Burnout Inventory was used to measure burnout among 125 staff members working in community residential facilities for persons with mental retardation in North Dakota. Results showed that a moderate degree of burnout was present for direct-care and supervisory staff members in each of the three subscales of the inventory. In addition, supervisory staff members showed significantly more burnout on the Emotional Exhaustion subscale and significantly less on the Personal Accomplishment subscale than did direct-care staff members. Results were discussed in light of previous findings.

Adult